Lečenje primarne imunološke trombocitopenije u eri novih vodiča i lekova
Ključne reči:
ITP, splenektomija, romiplostim, eltrombopag, rituksimab
Sažetak
Primarna imunološka trombocitopenija (ITP) predstavlja autoimunsko oboljenje koje se odlikuje izolovanom trombocitopenijom. Lečenje ITP-a često predstavlja izazov s obzirom na brojne terapijske modalitete. Izbor najprikladnijeg terapijskog pristupa za svakog pacijenta zavisi kako od bolesnikovog stanja i faze bolesti, tako i od bolesnikovih želja. Modaliteti prve terapijske linije su: kortikosteroidi, intravenski imunoglobulini i intravenski anti-D imunoglobulin. Sa druge strane, modaliteti druge terapijske linije se klasifikuju na hirurške (splenektomija) i nehirurške (agonisti trombopoetinskih receptora, rituksimab, fostamatinib, azatioprin, ciklofosfamid, ciklosporin A, hidroksihlorokin, mikofenolat mofetil, danazol, dapson, vinka alkaloidi). Međutim, i pored širokog spektra postojećih terapijskih modaliteta, neophodan je dalji razvoj lekova koji bi doveli do izlečenja i poboljšanja kvaliteta života svih obolelih od ITP-a.
Cilj ovog preglednog rada je upoznavanje čitalaca sa novim terapijskim pristupima u lečenju ITP-a odraslih.
Reference
Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113(11):2386-2393.
Terrell DR, Beebe LA, Vesely SK, Neas BR, Segal JB, George JN. The incidence of immune thrombocytopenic purpura in children and adults: A critical review of published reports. Am J Hematol. 2010;85(3):174-180.
Cooper N, Bussel J. The pathogenesis of immune thrombocytopaenic purpura. Br J Haematol. 2006;133(4):364-374.
Audia S, Mahévas M, Samson M, Godeau B, Bonnotte B. Pathogenesis of immune thrombocytopenia. Autoimmun Rev. 2017;16(6):620-632.
Provan D, Arnold DM, Bussel JB, Chong BH, Cooper N, Gernsheimer T, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019;3(22):3780-3817.
Piel-Julian ML, Mahévas M, Germain J, Languille L, Comont T, Lapeyre-Mestre M, et al. Risk factors for bleeding, including platelet count threshold, in newly diagnosed immune thrombocytopenia adults. J Thromb Haemost. 2018;16(9):1830-1842.
Khellaf M, Michel M, Schaeffer A, Bierling P, Godeau B. Assessment of a therapeutic strategy for adults with severe autoimmune thrombocytopenic purpura based on a bleeding score rather than platelet count. Haematologica. 2005;90(6):829-832.
Matzdorff A, Meyer O, Ostermann H, Kiefel V, Eberl W, Kühne T, et al. Immune Thrombocytopenia - Current Diagnostics and Therapy: Recommendations of a Joint Working Group of DGHO, ÖGHO, SGH, GPOH, and DGTI. Oncol Res Treat. 2018;41 Suppl 5:1-30.
Kitchens CS. Amelioration of endothelial abnormalities by prednisone in experimental thrombocytopenia in the rabbit. J Clin Invest. 1977;60(5):1129-1134.
Cooper N. State of the art - how I manage immune thrombocytopenia. Br J Haematol. 2017;177(1):39-54.
Mithoowani S, Gregory-Miller K, Goy J, Miller MC, Wang G, Noroozi N, et al. High-dose dexamethasone compared with prednisone for previously untreated primary immune thrombocytopenia: a systematic review and meta-analysis. Lancet Haematol. 2016;3(10):e489-e496.
Essilini A, Comont T, Germain J, Brun N, Dingremont C, Castel B, et al. Pretreatment with standard-dose intravenous methylprednisolone does not improve outcomes in newly diagnosed immune thrombocytopenia (ITP). Eur J Haematol. 2018;100(5):412-418.
Godeau B, Chevret S, Varet B, Lefrere F, Zini MF, Bassompierre F, et al. Intravenous immunoglobulin or high-dose methylprednisolone, with or without oral prednisone, for adults with untreated severe autoimmune thrombocytopenic purpura: a randomised, multicentre trial. Lancet. 2002;359(9300):23-29.
Neunert C, Terrell DR, Arnold DM, Buchanan G, Cines DB, Cooper N, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829-3866
Rice JB, White AG, Scarpati LM, Wan G, Nelson WW. Long-term Systemic Corticosteroid Exposure: A Systematic Literature Review. Clin Ther. 2017;39(11):2216-2229.
Bierling P, Godeau B. Intravenous immunoglobulin for autoimmune thrombocytopenic purpura. Hum Immunol. 2005;66(4):387-394.
Orbach H, Katz U, Sherer Y, Shoenfeld Y. Intravenous immunoglobulin: adverse effects and safe administration. Clin Rev Allergy Immunol. 2005;29(3):173-184.
Scaradavou A, Woo B, Woloski BM, Cunningham-Rundles S, Ettineger LJ, Aledort LM, et al. Intravenous anti-D treatment of immune thrombocytopenic purpura: experience in 272 patients. Blood. 1997;89(8):2689-2700.
Despotovic JM, Lambert MP, Herman JH, Gernsheimer TB, McCrae KR, Tarantino MD, et al. RhIG for the treatment of immune thrombocytopenia: consensus and controversy (CME). Transfusion. 2012;52(5):1126-1125.
Wong RSM, Saleh MN, Khelif A, Salama A, Portella MSO, Burgess P, et al. Safety and efficacy of long-term treatment of chronic/persistent ITP with eltrombopag: final results of the EXTEND study. Blood. 2017;130 (23):2527–2536.
Cines DB, Wasser J, Rodeghiero F, Chong BH, Steurer M, Provan D, et al. Safety and efficacy of romiplostim in splenectomized and nonsplenectomized patients with primary immune thrombocytopenia. Haematologica. 2017;102(8):1342-1351.
Ghanima W, Cooper N, Rodeghiero F, Godeau B, Bussel JB. Thrombopoietin receptor agonists: ten years later. Haematologica. 2019;104(6):1112-1123.
González-Porras JR, Godeau B, Carpenedo M. Switching thrombopoietin receptor agonist treatments in patients with primary immune thrombocytopenia. Ther Adv Hematol. 2019;10:2040620719837906. Published 2019 May 9.
Bussel, J.B. Avatrombopag. Br J Haematol. 2018;183(3): 342-343.
Xie C, Zhao H, Bao X, Fu H, Lou L. Pharmacological characterization of hetrombopag, a novel orally active human thrombopoietin receptor agonist. J Cell Mol Med. 2018;22(11):5367-5377.
Shirley M, McCafferty EH, Blair HA. Lusutrombopag: A Review in Thrombocytopenia in Patients with Chronic Liver Disease Prior to a Scheduled Procedure. Drugs. 2019;79(15):1689-1695.
Zaja F, Carpenedo M, Baratè C, Borchiellini A, Chiurazzi F, Finazzi G, et al. Tapering and discontinuation of thrombopoietin receptor agonists in immune thrombocytopenia: Real-world recommendations. Blood Rev. 2020;41:100647.
Chugh S, Darvish-Kazem S, Lim W, Crowther MA, Ghanima W, Wang G, et al. Rituximab plus standard of care for treatment of primary immune thrombocytopenia: a systematic review and meta-analysis. Lancet Haematol. 2015;2(2):e75-e81.
Stasi R, Stipa E, Forte V, Meo P, Amadori S. Variable patterns of response to rituximab treatment in adults with chronic idiopathic thrombocytopenic purpura. Blood. 2002;99(10):3872-3873.
Li Y, Shi Y, He Z, Chen Q, Liu Z, Yu L, et al. The efficacy and safety of low-dose rituximab in immune thrombocytopenia: a systematic review and meta-analysis. Platelets. 2019;30(6):690-697.
Marangon M, Vianelli N, Palandri F, Mazzucconi MG, Santoro C, Barcellini W, et al. Rituximab in immune thrombocytopenia: gender, age, and response as predictors of long-term response. Eur J Haematol. 2017;98(4):371-377.
Bussel J, Arnold DM, Grossbard E, Mayer J, Trelinski J, Homenda W, et al. Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo-controlled trials. Am J Hematol. 2018;93(7):921-930.
Lambert MP. Immunomodulatory Second-Line Therapies for Immune Thrombocytopenia. Hamostaseologie. 2019;39(3):266-271.
Chang H, Tang TC, Hung YS, Li PL, Kuo MC, Wu JH, et al. Immune thrombocytopenia: Effectiveness of frontline steroids and comparison of azathioprine, splenectomy, and rituximab as second-line treatment. Eur J Haematol. 2018;101(4):549-555.
Verlin M, Laros RK Jr, Penner JA. Treatment of refractory thrombocytopenic purpura with cyclophosphamine. Am J Hematol. 1976;1(1):97-104.
Emilia G, Morselli M, Luppi M, Longo G, Marasca R, Gandini G, et al. Long-term salvage therapy with cyclosporin A in refractory idiopathic thrombocytopenic purpura. Blood. 2002;99(4):1482-1485.
Mohammadpour F, Kargar M, Hadjibabaie M. The Role of Hydroxychloroquine as a Steroid-sparing Agent in the Treatment of Immune Thrombocytopenia: A Review of the Literature. J Res Pharm Pract. 2018;7(1):4-12.
Provan D, Moss AJ, Newland AC, Bussel JB. Efficacy of mycophenolate mofetil as single-agent therapy for refractory immune thrombocytopenic purpura. Am J Hematol. 2006;81(1):19-25.
Weber E, Reynaud Q, Fort R, Durupt S, Cathebras P, Durieu I, et al. Immunomodulatory treatments for persistent and chronic immune thrombocytopenic purpura: A PRISMA-compliant systematic review and meta-analysis of 28 studies. Medicine (Baltimore). 2017;96(37):e7534.
Park YH, Yi HG, Lee MH, Kim CS, Lim JH. Clinical efficacy and tolerability of vincristine in splenectomized patients with refractory or relapsed immune thrombocytopenia: a retrospective single-center study. Int J Hematol. 2016;103(2):180-188.
Kojouri K, Vesely SK, Terrell DR, George JN. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count responses, prediction of response, and surgical complications. Blood. 2004;104(9):2623-2634.
Chaturvedi S, Arnold DM, McCrae KR. Splenectomy for immune thrombocytopenia: down but not out. Blood. 2018;131(11):1172-1182.
Rodeghiero F. A critical appraisal of the evidence for the role of splenectomy in adults and children with ITP. Br J Haematol. 2018;181(2):183-195.
Bartholomew JR, Salgia R, Bell WR. Control of Bleeding in Patients With Immune and Nonimmune Thrombocytopenia With Aminocaproic Acid. Arch Intern Med. 1989;149(9):1959–1961.
Mayer B, Salama A. Successful treatment of bleeding with tranexamic acid in a series of 12 patients with immune thrombocytopenia. Vox Sang. 2017;112(8):767-772.
Rodeghiero F, Marranconi E. Management of immune thrombocytopenia in women: current standards and special considerations. Expert Rev Hematol. 2020;13(2):175-185.
Terrell DR, Beebe LA, Vesely SK, Neas BR, Segal JB, George JN. The incidence of immune thrombocytopenic purpura in children and adults: A critical review of published reports. Am J Hematol. 2010;85(3):174-180.
Cooper N, Bussel J. The pathogenesis of immune thrombocytopaenic purpura. Br J Haematol. 2006;133(4):364-374.
Audia S, Mahévas M, Samson M, Godeau B, Bonnotte B. Pathogenesis of immune thrombocytopenia. Autoimmun Rev. 2017;16(6):620-632.
Provan D, Arnold DM, Bussel JB, Chong BH, Cooper N, Gernsheimer T, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019;3(22):3780-3817.
Piel-Julian ML, Mahévas M, Germain J, Languille L, Comont T, Lapeyre-Mestre M, et al. Risk factors for bleeding, including platelet count threshold, in newly diagnosed immune thrombocytopenia adults. J Thromb Haemost. 2018;16(9):1830-1842.
Khellaf M, Michel M, Schaeffer A, Bierling P, Godeau B. Assessment of a therapeutic strategy for adults with severe autoimmune thrombocytopenic purpura based on a bleeding score rather than platelet count. Haematologica. 2005;90(6):829-832.
Matzdorff A, Meyer O, Ostermann H, Kiefel V, Eberl W, Kühne T, et al. Immune Thrombocytopenia - Current Diagnostics and Therapy: Recommendations of a Joint Working Group of DGHO, ÖGHO, SGH, GPOH, and DGTI. Oncol Res Treat. 2018;41 Suppl 5:1-30.
Kitchens CS. Amelioration of endothelial abnormalities by prednisone in experimental thrombocytopenia in the rabbit. J Clin Invest. 1977;60(5):1129-1134.
Cooper N. State of the art - how I manage immune thrombocytopenia. Br J Haematol. 2017;177(1):39-54.
Mithoowani S, Gregory-Miller K, Goy J, Miller MC, Wang G, Noroozi N, et al. High-dose dexamethasone compared with prednisone for previously untreated primary immune thrombocytopenia: a systematic review and meta-analysis. Lancet Haematol. 2016;3(10):e489-e496.
Essilini A, Comont T, Germain J, Brun N, Dingremont C, Castel B, et al. Pretreatment with standard-dose intravenous methylprednisolone does not improve outcomes in newly diagnosed immune thrombocytopenia (ITP). Eur J Haematol. 2018;100(5):412-418.
Godeau B, Chevret S, Varet B, Lefrere F, Zini MF, Bassompierre F, et al. Intravenous immunoglobulin or high-dose methylprednisolone, with or without oral prednisone, for adults with untreated severe autoimmune thrombocytopenic purpura: a randomised, multicentre trial. Lancet. 2002;359(9300):23-29.
Neunert C, Terrell DR, Arnold DM, Buchanan G, Cines DB, Cooper N, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829-3866
Rice JB, White AG, Scarpati LM, Wan G, Nelson WW. Long-term Systemic Corticosteroid Exposure: A Systematic Literature Review. Clin Ther. 2017;39(11):2216-2229.
Bierling P, Godeau B. Intravenous immunoglobulin for autoimmune thrombocytopenic purpura. Hum Immunol. 2005;66(4):387-394.
Orbach H, Katz U, Sherer Y, Shoenfeld Y. Intravenous immunoglobulin: adverse effects and safe administration. Clin Rev Allergy Immunol. 2005;29(3):173-184.
Scaradavou A, Woo B, Woloski BM, Cunningham-Rundles S, Ettineger LJ, Aledort LM, et al. Intravenous anti-D treatment of immune thrombocytopenic purpura: experience in 272 patients. Blood. 1997;89(8):2689-2700.
Despotovic JM, Lambert MP, Herman JH, Gernsheimer TB, McCrae KR, Tarantino MD, et al. RhIG for the treatment of immune thrombocytopenia: consensus and controversy (CME). Transfusion. 2012;52(5):1126-1125.
Wong RSM, Saleh MN, Khelif A, Salama A, Portella MSO, Burgess P, et al. Safety and efficacy of long-term treatment of chronic/persistent ITP with eltrombopag: final results of the EXTEND study. Blood. 2017;130 (23):2527–2536.
Cines DB, Wasser J, Rodeghiero F, Chong BH, Steurer M, Provan D, et al. Safety and efficacy of romiplostim in splenectomized and nonsplenectomized patients with primary immune thrombocytopenia. Haematologica. 2017;102(8):1342-1351.
Ghanima W, Cooper N, Rodeghiero F, Godeau B, Bussel JB. Thrombopoietin receptor agonists: ten years later. Haematologica. 2019;104(6):1112-1123.
González-Porras JR, Godeau B, Carpenedo M. Switching thrombopoietin receptor agonist treatments in patients with primary immune thrombocytopenia. Ther Adv Hematol. 2019;10:2040620719837906. Published 2019 May 9.
Bussel, J.B. Avatrombopag. Br J Haematol. 2018;183(3): 342-343.
Xie C, Zhao H, Bao X, Fu H, Lou L. Pharmacological characterization of hetrombopag, a novel orally active human thrombopoietin receptor agonist. J Cell Mol Med. 2018;22(11):5367-5377.
Shirley M, McCafferty EH, Blair HA. Lusutrombopag: A Review in Thrombocytopenia in Patients with Chronic Liver Disease Prior to a Scheduled Procedure. Drugs. 2019;79(15):1689-1695.
Zaja F, Carpenedo M, Baratè C, Borchiellini A, Chiurazzi F, Finazzi G, et al. Tapering and discontinuation of thrombopoietin receptor agonists in immune thrombocytopenia: Real-world recommendations. Blood Rev. 2020;41:100647.
Chugh S, Darvish-Kazem S, Lim W, Crowther MA, Ghanima W, Wang G, et al. Rituximab plus standard of care for treatment of primary immune thrombocytopenia: a systematic review and meta-analysis. Lancet Haematol. 2015;2(2):e75-e81.
Stasi R, Stipa E, Forte V, Meo P, Amadori S. Variable patterns of response to rituximab treatment in adults with chronic idiopathic thrombocytopenic purpura. Blood. 2002;99(10):3872-3873.
Li Y, Shi Y, He Z, Chen Q, Liu Z, Yu L, et al. The efficacy and safety of low-dose rituximab in immune thrombocytopenia: a systematic review and meta-analysis. Platelets. 2019;30(6):690-697.
Marangon M, Vianelli N, Palandri F, Mazzucconi MG, Santoro C, Barcellini W, et al. Rituximab in immune thrombocytopenia: gender, age, and response as predictors of long-term response. Eur J Haematol. 2017;98(4):371-377.
Bussel J, Arnold DM, Grossbard E, Mayer J, Trelinski J, Homenda W, et al. Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo-controlled trials. Am J Hematol. 2018;93(7):921-930.
Lambert MP. Immunomodulatory Second-Line Therapies for Immune Thrombocytopenia. Hamostaseologie. 2019;39(3):266-271.
Chang H, Tang TC, Hung YS, Li PL, Kuo MC, Wu JH, et al. Immune thrombocytopenia: Effectiveness of frontline steroids and comparison of azathioprine, splenectomy, and rituximab as second-line treatment. Eur J Haematol. 2018;101(4):549-555.
Verlin M, Laros RK Jr, Penner JA. Treatment of refractory thrombocytopenic purpura with cyclophosphamine. Am J Hematol. 1976;1(1):97-104.
Emilia G, Morselli M, Luppi M, Longo G, Marasca R, Gandini G, et al. Long-term salvage therapy with cyclosporin A in refractory idiopathic thrombocytopenic purpura. Blood. 2002;99(4):1482-1485.
Mohammadpour F, Kargar M, Hadjibabaie M. The Role of Hydroxychloroquine as a Steroid-sparing Agent in the Treatment of Immune Thrombocytopenia: A Review of the Literature. J Res Pharm Pract. 2018;7(1):4-12.
Provan D, Moss AJ, Newland AC, Bussel JB. Efficacy of mycophenolate mofetil as single-agent therapy for refractory immune thrombocytopenic purpura. Am J Hematol. 2006;81(1):19-25.
Weber E, Reynaud Q, Fort R, Durupt S, Cathebras P, Durieu I, et al. Immunomodulatory treatments for persistent and chronic immune thrombocytopenic purpura: A PRISMA-compliant systematic review and meta-analysis of 28 studies. Medicine (Baltimore). 2017;96(37):e7534.
Park YH, Yi HG, Lee MH, Kim CS, Lim JH. Clinical efficacy and tolerability of vincristine in splenectomized patients with refractory or relapsed immune thrombocytopenia: a retrospective single-center study. Int J Hematol. 2016;103(2):180-188.
Kojouri K, Vesely SK, Terrell DR, George JN. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count responses, prediction of response, and surgical complications. Blood. 2004;104(9):2623-2634.
Chaturvedi S, Arnold DM, McCrae KR. Splenectomy for immune thrombocytopenia: down but not out. Blood. 2018;131(11):1172-1182.
Rodeghiero F. A critical appraisal of the evidence for the role of splenectomy in adults and children with ITP. Br J Haematol. 2018;181(2):183-195.
Bartholomew JR, Salgia R, Bell WR. Control of Bleeding in Patients With Immune and Nonimmune Thrombocytopenia With Aminocaproic Acid. Arch Intern Med. 1989;149(9):1959–1961.
Mayer B, Salama A. Successful treatment of bleeding with tranexamic acid in a series of 12 patients with immune thrombocytopenia. Vox Sang. 2017;112(8):767-772.
Rodeghiero F, Marranconi E. Management of immune thrombocytopenia in women: current standards and special considerations. Expert Rev Hematol. 2020;13(2):175-185.
Objavljeno
2020/12/31
Broj časopisa
Rubrika
Mini pregledni članak